Myocardial and vascular lesions were found in dogs and in miniature swine treated with high doses of minoxidil, a vasodilating antihypertensive agent. The myocardial lesions consisted of focal areas of necrosis and were localized mainly to the regions of the left ventricular papillary muscles. These lesions were considered to be hypoxic in origin and to reflect minoxidil-induced changes in the amount and distribution of regional coronary blood flow, together with increased demands for oxygen consumption. The vascular lesions mainly affected the small arterioles. They were characterized by endothelial damage, intramural accumulation of red blood cells and platelets and by a perivascular inflammatory reaction. They were thought to result from overstretching of dilated arterioles.